Preparation of murine liver tumor vaccine modified by Flt3 ligand and its in vivo antitumor activity

Objective:To prepare murine liver tumor vaccine by infection of recombinant adenoviral vector carrying murine Flt3 ligand and to observe its in vivo antitumor activity. Methods:The infection efficacy was measured by GFP expression 48 h following infection of Hepa1-6, and the amount of mFL in supernatant at day 0, 2, 4, 6, 8 was measured by ELISA. The cells number was counted daily for 14 d. Modified Hepa1-6 cells (5×10 6) were subcutaneously inoculated into C57BL/6 mice, and they were rechallenged by 2×10 6 wild-type Hepa1-6 cells or syngenic EL4 cells 4 weeks later. The tumor volume was measured twice a week. Results:Adenoviral vectors efficiently infected Hepa1-6 cells in vitro, and led to the secretion of high levels of mFL protein (71.1±6.3 ng/ml) 2 d after infection. The in vitro growth rate of AdmFL modified Hepa1-6 cells was not affected, while the in vivo tumorigenesis was significantly decreased compared with that of control vector modified Hepa1-6. Rechallenge of the mice 4 weeks after administration of Ad mFL with the parental Hepa1-6 cells resulted in significant inhibition of tumor growth, while there was no difference when rechallenged with EL4. Conclusion:The liver cancer cells modified by recombinant adenoviral vector carrying murine flt3 ligand can decease tumorigenesis and elicit specific immunological protection, it can be used as an effective liver tumor vaccine.